A chemiluminescence (CL) method has been developed for the determination of Hydroxyzine (Hyd) and its metabolite Cetirizine (Cet). The method is based on sensitizing effect of Cet and Hyd on the weak CL reaction between Ru(phen)32+ and acidic Ce(IV). A mechanism for the CL reaction has been proposed on the basis of UV-Vis, fluorescent and CL spectra. By using the recommended procedure, the calibration graphs were linear over 0.14 to 14.0 μg mL-1 (r2=0.9966) and 0.07 to 10.0 μg mL-1 (r2=0.9984) for Hyd and Cet, respectively. The limits of detections were 0.06 μg mL-1 and 0.03 μg mL-1 for Hyd and Cet, respectively. The percent of relative standard deviations (n=11) for 1.0 μg mL-1 of Hyd and 0.74 μg mL-1 of Cet were 4.5 and 2.3%, respectively. The broad time profile of Hyd and Cet allowed us to determine Hyd contents in plasma samples with minimum blank interferences from cysteine and ascorbic acid. The method has been satisfactorily used for the determination of Hyd and Cet in syrups, tablets and human plasma.